On coasts, the tides determine the rhythm of events. At low tide, boats remain on land; at high tide, the way out to sea is cleared for them again. On Earth, the tides are mainly generated by the moon. Its gravitational pull causes an accumulation of water in the ocean region below, which is then missing in surrounding regions and thus accounts for the low tide. Although this deformation of the ocean causes striking differences in level in many places, it is hardly recognisable from space.

On the planet WASP-103b, tides are much more extreme. The planet orbits its star in just one day and is deformed by the strong tidal forces so drastically, that its appearance resembles a rugby ball. This is shown by a new study involving researchers from the Universities of Bern and Geneva as well as the National Centre of Competence in Research (NCCR) PlanetS, published today in the scientific journal Astronomy & Astrophysics. This finding was made possible thanks to observations with the CHEOPS space telescope. CHEOPS is a joint mission of the European Space Agency (ESA) and Switzerland, led by the University of Bern in collaboration with the University of Geneva.

A groundbreaking measurement

The planet WASP-103b is located in the constellation Hercules, is almost twice the size of Jupiter, has one and a half times its mass and is about fifty times closer to its star than Earth is to the Sun. “Because of its great proximity to its star, we had already suspected that very large tides are caused on the planet. But, we had not yet been able to verify this,” explains study co-author Yann Alibert, professor of astrophysics at the University of Bern and member of the NCCR PlanetS.

The NASA/ESA Hubble Space Telescope and NASA’s Spitzer Space Telescope had already observed the planet. In combination with the high precision and pointing flexibility of CHEOPS, these observations enabled the researchers to measure the tiny signal of the tidal deformation of the planet light years away. In doing so, they took advantage of the fact that the planet dims the light of the star slightly each time it passes in front of it. “After observing several such so-called “transits,” we were able to measure the deformation. It’s incredible that we were able to do this — it’s the first time such an analysis has been done,” reports Babatunde Akinsanmi, a researcher at the University of Geneva, co-author of the study and NCCR PlanetS associate.

The planet is inflated

The researchers’ results not only allow conclusions to be drawn about the shape of the planet, but also about its interior. This is because the team was also able to derive a parameter called the “Love number” (named after the British mathematician Augustus E. H. Love) from the transit light curve of WASP-103b. It indicates how the mass is distributed within the planet and thus also gives clues about its inner structure. “The resistance of a material to deformation depends on its composition,” explains Akinsanmi. “We can only see the tides on Earth in the oceans. The rocky part doesn’t move that much. Therefore, by measuring how much the planet is deformed, we can determine how much of it is made up of rock, gas or water.”

WASP-103b’s Love number is like Jupiter’s, our Solar System’s biggest gas giant. It suggests that the internal structures of WASP-103b and Jupiter are similar — even though WASP-103b is twice as large. “In principle, we would expect a planet with 1.5 times the mass of Jupiter to be about the same size. Therefore, WASP-103b must be highly inflated due to heating by its nearby star, and perhaps other mechanisms,” says Monika Lendl, professor of astronomy at the University of Geneva and co-author of the study.

However, since the measurement uncertainty in the Love number is still quite high, future observations with CHEOPS and the James Webb Space Telescope will be needed to decipher the details of the tidal deformation and internal structure of WASP-103b and comparable exoplanets. “This would improve our understanding of these so-called ‘hot Jupiters’ and allow a better comparison between them and giant planets in the Solar System,” Lendl concludes.

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In a new study, Clay Clark, chair and professor of biology at The University of Texas at Arlington, explores the ancestry of a class of enzymes responsible for killing cells. These enzymes, known as effector caspases, provide insight into the process of cell death and how it can be manipulated in disease states.

“If drug developers want to target a cancer cell, they could activate the caspases to perform their normal function of killing cells,” Clark said. “But we first need to isolate the caspases of cancer cells and not alter their activity in normal cells. The question is, how can we target the activity of the tumor cell without disturbing its healthy neighbors.”

The study, “Evolution of the folding landscape of effector caspases,” appears in the Journal of Biological Chemistry. In it, Clark and co-author Suman Shrestha, UTA alumnus and postdoctoral fellow at Princess Margaret Cancer Center, look to the past for answers.

Cells have had effector caspases since organisms called eukaryotes emerged more than a billion years ago. Over time, the caspases evolved from one to 12 proteins that serve various functions during cell growth and division. To understand their evolution, Clark’s laboratory used a computational method called ancestral state reconstruction to recreate a 650-million-year-old protein sequence of an ascendant of caspases 3, 6 and 7.

Caspases are the central components of apoptosis. In cancerous states, cells turn off caspases and circumvent the cell death process. A goal of Clark’s research is to understand how effector caspases work in healthy conditions. Once the proteins’ normal function is understood, Clark’s team could discover methods to activate them in disease states to destroy abnormal cells while preserving healthy ones.

By examining the ancestor’s characteristics and tracing the protein’s evolution into multiple members, Clark’s team discovered commonalities and differences among caspases 3, 6 and 7 that could allow for the isolated activation of proteins in tumor cells without disrupting the activity of healthy cells.

Morteza Khaledi, dean of the College of Science, said the results of the study will advance humanity’s battle to mitigate the effects of cancer.

“By employing the innovative methods of ancestral state reconstruction, Dr. Clark’s team has discovered vital information about the essential building blocks for healthy human bodies,” Khaledi said. “The knowledge uncovered in this study provides another weapon in our fight against cancer.”

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Materials provided by University of Texas at Arlington. Original written by Linsey Retcofsky. Note: Content may be edited for style and length.

The study, which appears in Environment International, was among the first to examine the impact that phthalates, added to plastics to increase flexibility, have on the placental corticotropin releasing hormone (pCRH) that is produced by the placenta and increases throughout the course of pregnancy. The hormone plays an important role in promoting the onset of labor, but when levels are high or rise rapidly earlier in pregnancy, it may contribute to preterm birth and fetal growth problems as well as high blood pressure, diabetes, and postpartum depression.

“We are all exposed to phthalates in our environment through the products we use and the foods we eat,” says Emily S. Barrett, an associate professor at the Rutgers School of Public Health and member of the Environmental and Occupational Health Sciences Institute. “Our findings show that these chemicals may alter the production of essential placental hormones, which has important implications for the course of pregnancy as well as subsequent child health and development.”

The researchers analyzed data from 1,018 low-risk pregnant women carrying single fetuses at two time points, mid- and late pregnancy.

They found that the presence of various phthalates was associated with higher pCRH hormone levels in mid-pregnancy, but lower pCRH later in pregnancy. These levels were strongest in women who developed pregnancy complications like gestational diabetes and high blood pressure, suggesting that women who develop complications may be particularly vulnerable to this hormonal disruption. This is among the first and largest study so far to examine how these chemicals and the connection with pCRH disrupt the function of the endocrine system, which is especially delicate during pregnancy.

“Associations between phthalates and pCRH among women with pregnancy complications grew stronger across the course of pregnancy. We know very little about how women with pregnancy complications are affected by environmental exposures. This study sets the stage for future research in that area,” Barrett said.

pCRH produced by the placenta is identical in structure to corticotropin-releasing hormone (CRH) produced by the brain when responding to stress. While this study did not find that women who had experienced childhood traumas were any more vulnerable to the hormone-disrupting effects of phthalates, earlier research found that pCRH levels were higher in women who have experienced childhood trauma suggesting that traumatic events may impact pregnancy decades later.

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Materials provided by Rutgers University. Original written by Michelle Edelstein. Note: Content may be edited for style and length.

Liver cancer is the sixth most common cancer and the third leading cause of cancer related death worldwide. Despite the promising initial response to molecularly targeted therapies, tumours are often susceptible to developing drug resistance. It is no exception for sorafenib, the mainstay of treatment for HCC, and the available treatment options are very limited. Drug combination is a strategy for expanding options for cancer treatment to reduce the risk of drug resistance and tumour relapse that often arises in standalone treatment. The simplicity and precision of CRISPR-Cas9 that uses guide ribonucleic acids (RNAs) to knockout any genes in the genome make it a great tool to identify targets for potential drug discovery and development.

Utilising the screening platform of CombiGEM-CRISPR v2.0 to generate multiplexable gene knockouts, this study rapidly characterised the survival of cancer cells following dual-genetic knockouts in a pool of cells linked with DNA barcodes specifying the types of genetic alterations they carry. Instead of using conventional drug screening array that requires handling of numerous independent multi-wells, this platform only requires a simple experimental setup as the number of DNA barcodes carried by a large population of cells grown in the same culture dish could be counted in high volume via high-throughput sequencing technologies. Through screening genes and their combinations from which hits can be translated directly into drug combinations using existing drugs, non-conventional drugs and drug combinations could be discovered and repurposed for treating cancers.

Through a combinatorial CRISPR-Cas9 screen focusing on a set of druggable targets of which their expressions are upregulated in HCC cancer stem cells, the HKUMed research team identified two combinations harbouring a common target known as NMDAR1 and its paired targets are two kinases (FLT4 and FGFR3) of which both their corresponding drug inhibitor is the first line sorafenib. Specifically, genetically ablation of the identified gene combinations inhibits HCC cells’ growth and self-renewal ability. Based on The Cancer Genome Atlas database, the research team also unveiled the clinical significance of NMDAR1 in HCC, where HCC patients with low level of NMDAR1 expression show better survival outcomes.

The team also revealed the enhanced inhibition effect of the corresponding drug combination and their underlying molecular mechanisms. Co-administration of ifenprodil and sorafenib remarkably reduced the cell growth and stemness in multiple HCC cell lines, patient-derived organoids and tumour xenograft models. Additionally, the team also showed that the upregulation of unfolded protein response, triggering of cell-cycle arrest, and downregulation of genes associated with WNT-signaling and stemness could account for the enhanced effects of the drug combination.

Ifenprodil has been used as a vasodilator in countries including Japan and France with known safety history in humans. Combined with the first line sorafenib, the HKUMed research team has successfully demonstrated this two-drug regimen profoundly suppressed HCC cells’ growth and self-renewal ability.

‘Successful drug repurposing saves the cost and time that otherwise would be needed for developing new therapeutic agents with uncertain efficacy and safety profile. It also increases the chance of clinical translation of the findings from bench to bedside as the identified drug combination could be readily tested in future trials for treating HCC. Our work has identified a potentially useful drug combination to be further tested for the treatment of HCC patients from approved drugs, which could possibly save or prolong patients’ life,’ said Dr Stephanie Ma, Associate Professor of the School of Biomedical Sciences, HKUMed, who co-led the study.

‘The application of the CombiGEM-CRISPR v2.0 platform has broadened our scope in search for effective combinations of actionable targets and approved/repurposed drugs for HCC in a rapid and simple manner, and could be extended to other cancers and diseases,’ added Dr Alan Wong Siu-lun, Assistant Professor of the School of Biomedical Sciences, HKUMed, who co-led the research.

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Megaripples are sand waves with wavelengths in the metre range, between ordinary beach ripples (centimetres) and dunes (ten to 100 metres). They are commonly found on earth and Mars. Their sand consists of a unique mixture of coarse and fine grains. “This mixture always looks similar, but is never identical because of the turbulent winds,” explained Professor Klaus-Dieter Kroy of the Institute of Theoretical Physics at Leipzig University, one of the study’s leaders.

Among this diversity, the interdisciplinary team of geomorphologists and physicists from three universities in Germany, Israel and China has now discovered an unexpectedly uniform characteristic of the underlying sand transport process, one that had previously eluded decades of field studies. In their analysis of sand sample data from around the world, the researchers compared the frequencies of all sizes of shifting grains and divided the diameter of the coarsest grains and of the rarest fine grains for each sample. A surprisingly consistent number emerged, as Kroy pointed out. That number can now be used to decide more reliably which category newly discovered sand ripples belong to — as predicted by the team’s theoretical calculations — and by which physical transport process they were formed.

The international team also hopes that its discovery could help in the future to better explain the formation of some mysterious new sand waves recently observed on Mars. Katharina Tholen, a doctoral researcher at Leipzig University and lead author of the study, said: “If we were able to use prevailing atmospheric conditions to explain the origin and migration of terrestrial and extraterrestrial sand waves, this would be an important step. It might then be possible to evaluate the sand structures we are currently observing, for example on Mars or in fossils and remote locations on earth, as complex archives of past climatic conditions.”

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While many dinosaurs likely lived in groups, at least some ankylosaurs seemed to prefer a lonesome life because of an inferior sense of hearing. That’s what the scientists from the universities of Greifswald and Vienna concluded when they examined the braincase of the Austrian dinosaur with a high-resolution computer tomograph to produce a digital three-dimensional cast.

Fossil braincases, which once housed the brain and other neurosensory tissues, are rare but important for science because these structures can provide insights into the lifestyle of a given animal. For example, the inner ears can hint to auditory capacities and skull orientation.

Struthiosaurus austriacus is a comparably small nodosaurid from the Late Cretaceous (80 Ma) of Austria and comes from a locality near Muthmannsdorf, south of Vienna. The fossil remains of this dinosaur already belonged to the collection of the Institute for Paleontology in Vienna in the 19th century. For their study, Marco Schade (University of Greifswald), Cathrin Pfaff (University of Vienna) and their colleagues examined the tiny (50 mm) braincase to reveal new details of the anatomy and lifestyle of Struthiosaurus austriacus. With these data, it was possible to learn more about its sense of equilibrium and audition.

The results of this study show that Struthiosaurus’ brain was very similar to the brains of its close relatives. For example, the flocculus, an evolutionary old part of the brain, was very small. The flocculus is important for the fixation of the eyes during motions of the head, neck and whole body, which can be very useful if such an animal was trying to target potential competitors or aggressors. “In contrast to its Northamerican relative Euoplocephalus, which had a tail club and a clear flocculus on the brain cast, Struthiosaurus austriacus may rather relied on its body armor for protection,” says Marco Schade. Together with the form of the semicircular canals in the inner ear, this hints towards an exceptionally sluggish lifestyle of this Austrian plant eater. Furthermore, the scientists found the — so far — shortest lagena of a dinosaur. The lagena is the part of the inner ear where audition takes place and its size can help to infer auditory capacities. This study delivers new insights into the evolutionary history of dinosaurs and their world, in which Europe was largely submerged in the ocean.

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